Ketamine and Xylazine Effects in Murine Model of Acute Pancreatitis
Ketamine and xylazine (Ket/Xyl) are anesthetic agents that target neural pathways and are commonly used in combination in mouse studies. Since neural pathways can modulate acute pancreatitis severity we asked if Ket/Xyl affect disease severity. C57BL/6 mice were treated with six hourly injections of cerulein to induce mild acute pancreatitis. Mice were also treated with and without ketamine, xylazine, and Ket/Xyl prior to pancreatitis induction in vivo and in vitro. Ket/Xyl pre-treatment in vivo increased select parameters of pancreatitis severity such as trypsin activity and edema; these effects were predominantly mediated by xylazine. Ket/Xyl also changed markers of autophagy. These in vivo effects of Ket/Xyl were not attenuated by atropine. The drugs had no little to no effect on pancreatitis responses in isolated pancreatic cells or lobules. These findings suggest that Ket/Xyl administration can have substantial effect on acute pancreatitis outcomes through non-muscarinic neural pathways. Given wide-spread use of this anesthetic combination in experimental animal models, future studies of inflammation and injury using Ket/Xyl should be interpreted with caution.